Cerebellar rTMS Research Articles

Cerebellar rTMS in PSP: a Double-Blind Sham-Controlled Study Using Mobile Health Technology

There are no effective treatments in progressive supranuclear palsy (PSP). The aim of this study was to test the efficacy of theta burst repetitive transcranial magnetic stimulation (rTMS) on postural instability in PSP. Twenty PSP patients underwent a session of sham or real cerebellar rTMS in a crossover design. Before and after stimulation, static balance was evaluated with instrumented (lower back accelerometer, Rehagait®, Hasomed, Germany) 30-s trials in semitandem and tandem positions. In tandem and semitandem tasks, active stimulation was associated with increase in time without falls (both p=0.04). In the same tasks, device-extracted parameters revealed significant improvement in area (p=0.007), velocity (p=0.005), acceleration and jerkiness of sway (p=0.008) in real versus sham stimulation. Cerebellar rTMS showed a significant effect on stability in PSP patients, when assessed with mobile digital technology, in a double-blind design. These results should motivate larger and longer trials using non-invasive brain stimulation for PSP patients.

Cerebellar rTMS and PAS effectively induce cerebellar plasticity

Non-invasive brain stimulation techniques including repetitive transcranial magnetic stimulation (rTMS), continuous theta-burst stimulation (cTBS), paired associative stimulation (PAS), and transcranial direct current stimulation (tDCS) have been applied over the cerebellum to induce plasticity and gain insights into the interaction of the cerebellum with neo-cortical structures including the motor cortex. We compared the effects of 1 Hz rTMS, cTBS, PAS and tDCS given over the cerebellum on motor cortical excitability and interactions between the cerebellum and dorsal premotor cortex / primary motor cortex in two within subject designs in healthy controls. In experiment 1, rTMS, cTBS, PAS, and tDCS were applied over the cerebellum in 20 healthy subjects. In experiment 2, rTMS and PAS were compared to sham conditions in another group of 20 healthy subjects. In experiment 1, PAS reduced cortical excitability determined by motor evoked potentials (MEP) amplitudes, whereas rTMS increased motor thresholds and facilitated dorsal premotor-motor and cerebellum-motor cortex interactions. TDCS and cTBS had no significant effects. In experiment 2, MEP amplitudes increased after rTMS and motor thresholds following PAS. Analysis of all participants who received rTMS and PAS showed that MEP amplitudes were reduced after PAS and increased following rTMS. rTMS also caused facilitation of dorsal premotor-motor cortex and cerebellum-motor cortex interactions. In summary, cerebellar 1 Hz rTMS and PAS can effectively induce plasticity in cerebello-(premotor)-motor pathways provided larger samples are studied.

The Effects of Midline Cerebellar rTMS on Human Pharyngeal Cortical Activity in the Intact Swallowing Motor System

We sought to compare the effects of 10 Hz cerebellar vermis (vs. unilateral hemispheric and sham) repetitive transcranial magnetic stimulation (rTMS) on cortical neuroelectrical activity and thereafter 10 Hz cerebellar vermis (vs. sham) rTMS on swallowing behaviour. Healthy participants (n = 25) were randomly allocated to receive vermis, unilateral hemisphere or sham 10 Hz cerebellar rTMS. Recordings were made using pharyngeal electromyography and manometry catheters, obtaining motor-evoked potentials (MEPs) and pressure recordings. The amplitudes of MEPs elicited using single-pulse TMS delivered to the pharyngeal areas of the motor cortex bilaterally were measured pre- and post-cerebellar stimulation. As in previous studies, abductor policis brevis (APB) MEPs were measured to assess post-rTMS modulation specificity. Swallowing was assessed using a swallowing accuracy task. Measurements were made at baseline and 15-min intervals for an hour post-intervention. Measurements involved TMS being used to elicit 10 MEPs bilaterally over the pharyngeal areas of the motor cortex, over the APB cortical representation adjacent to the pharyngeal area with the lowest resting motor threshold and 5 MEPs bilaterally over pharyngeal areas of the cerebellar hemispheres. Swallowing accuracy was assessed by giving participants 10 attempts to swallow and hit a digital target. Cerebellar vermis rTMS caused significant suppression of cortical pharyngeal MEP amplitudes compared with unilateral rTMS and sham (P = 0.0005, 0.002). APB and cerebellar MEP amplitudes were unaffected as were pharyngeal and APB MEP latencies. Following cerebellar vermis rTMS there was a significant reduction in swallowing accuracy compared with sham (P = 0.001). Our findings demonstrate cerebellar vermis rTMS exerts a suppressive effect on pharyngeal motor cortical activity and swallowing behaviour.

The effects of unilateral and bilateral cerebellar rTMS on human pharyngeal motor cortical activity and swallowing behavior

The cerebellum is recognised to bilaterally modulate sensorimotor function and has recently been shown to play a role in swallowing. Unilateral cerebellar repetitive trans-cranial magnetic stimulation (rTMS) excites corticobulbar motor pathways to the pharynx but the effects of bilateral versus unilateral cerebellar rTMS on these pathways are unknown. In this three-part cross-over study, healthy participants (n = 13) were randomly allocated to receive unilateral or bilateral 10 Hz cerebellar rTMS. Participants were intubated with pharyngeal electromyography and/or manometry catheters for motor evoked potentials (MEPs) and pressure recordings. In part 1 of the study, single pulse TMS was used to measure baseline motor cortical pharyngeal MEP (PMEP) and hemispheric cerebellar MEP (CMEP) amplitudes, before cerebellar rTMS was administered. Repeat measures of PMEP amplitude were performed at 15-min intervals for an hour post unilateral and bilateral rTMS. Thereafter, in two further studies, a cortical ‘virtual lesion’ (V/L) was applied prior to cerebellar rTMS with pre and post PMEPs (part 2) and measurements of swallowing accuracy (part 3) using a behavioural task. Compared to baseline, unilateral and bilateral cerebellar rTMS provoked increases in pharyngeal cortical excitation (P = 0.028, 0.0005, respectively). Bilateral rTMS was significantly more effective than unilateral in causing cortical excitation (P = 0.0005) and in reversing the suppressive neurological (P = 0.0005) and behavioural (P = 0.0005) effects of a cortical V/L. Our findings suggest bilateral cerebellar rTMS has greater facilitatory effects on corticobulbar motor pathways to the pharynx than unilateral stimulation with the potential to be a more effective clinical therapy if its effects are reproduced in populations with neurogenic dysphagia.

P159 The effects of midline cerebellar rTMS on human pharyngeal cortical activity in the intact swallowing motor system

P159 The effects of midline cerebellar rTMS on human pharyngeal cortical activity in the intact swallowing motor system

Cerebellar rTMS Theta Burst for Dual-task Walking in Parkinson's Disease

Cerebellar rTMS Theta Burst for Dual-task Walking in Parkinson's Disease

An Exploration of the Application of Noninvasive Cerebellar Stimulation in the Neuro-rehabilitation of Dysphagia after Stroke (EXCITES) Protocol

Background: Poststroke dysphagia is common, associated with a poor outcome and has no definitive treatments. Repetitive transcranial magnetic stimulation (rTMS) targeting the cerebellum is a noninvasive technique requiring minimal physical or cognitive input from the patient, and has been shown to induce positive swallow-related brain changes in physiological studies as measured by increased cortical excitability. Aim: To explore in patients with acute/sub-acute poststroke dysphagia: (1) the feasibility and immediate effect; and (2) the optimal dose for long-term benefit, of cerebellar rTMS in patients with dysphagia in acute/sub-acute stroke. Methods: Two double-blind sham-controlled randomized phase II trials. Participants will be recruited from stroke units in Nottingham and Greater Manchester. Dysphagia will be confirmed via baseline videofluoroscopy (VFS). Participants will be blinded to treatment and receive cerebellar rTMS or sham stimulation: (1) single treatment of (10Hz, 250 pulse) in 24 participants; (2) daily for 3 days, twice-daily for 5 days, or twice-daily sham treatment for 5 days, in 48 participants. Results: The severity of dysphagia will be assessed with VFS, using the penetration aspiration scale (PAS) at: (1) 1-hour, (2) 2-weeks, post-treatment. Additional comparative measures will be taken from: (1) pharyngeal motor evoked potential (MEP) amplitudes, (2) the functional oral intake score and dysphagia severity rating scale. Conclusions: If these studies demonstrate feasibility and identify optimal dosing, further trials to assess the safety and efficacy of cerebellar rTMS as a treatment for poststroke dysphagia will be warranted.

Cerebellum-mediated trainability of eye and head movements for dynamic gazing.

ObjectiveTo investigate whether gaze stabilization exercises (GSEs) improve eye and head movements and whether low-frequency cerebellar repetitive transcranial magnetic stimulation (rTMS) inhibits GSE trainability.Methods25 healthy adults (real rTMS, n = 12; sham rTMS, n = 13) were recruited. Real or sham rTMS was performed for 15 min (1 Hz, 900 stimulations). The center of the butterfly coil was set 1 cm below the inion in the real rTMS. Following stimulation, 10 trials of 1 min of a GSE were conducted at 1 min intervals. In the GSE, the subjects were instructed to stand upright and horizontally rotate their heads according to a beeping sound corresponding to 2 Hz and with a gaze point ahead of them. Electrooculograms were used to estimate the horizontal gaze direction of the right eye, and gyroscopic measurements were performed to estimate the horizontal head angular velocity during the GSE trials. The percentage change from the first trial of motion range of the eye and head was calculated for each measurement. The percent change of the eye/head range ratio was calculated to assess the synchronous changes of the eye and head movements as the exercise increased.ResultsBayesian two-way analysis of variance showed that cerebellar rTMS affected the eye motion range and eye/head range ratio. A post hoc comparison (Bayesian t-test) showed evidence that the eye motion range and eye/head range ratio were reduced in the fifth, sixth, and seventh trials compared with the first trial sham stimulation condition.ConclusionsGSEs can modulate eye movements with respect to head movements, and the cerebellum may be associated with eye–head coordination trainability for dynamic gazing during head movements.

Cerebellar repetitive transcranial magnetic stimulation (rTMS) for essential tremor: A double-blind, sham-controlled, crossover, add-on clinical trial

BackgroundThere is controversial evidence about the effect of cerebellar low-frequency stimulation in patients with essential tremor (ET). ObjectivesIn this study we assessed safety and effectiveness of 1 Hz (low-frequency) cerebellar repetitive transcranial magnetic stimulation (rTMS) on tremor severity in patients with essential tremor in a sham-controlled crossover trial. MethodsA total of 23 patients assigned into two groups to receive either sham (n = 10) or rTMS (n = 13) treatment, with crossing over after a two-month washout period. Intervention consisted of 900 pulses of 1 Hz rTMS at 90% resting motor threshold or the same protocol of sham stimulation over each cerebellar hemisphere for 5 consecutive days. Tremor severity was assessed by Fahn-Tolosa-Marin (FTM) scale at baseline and at days 5, 12 and 30 after intervention. The FTM consists of 3 subscales including tremor severity rating, performance of motor tasks, and functional disability. Carry-over and treatment effects were analyzed using independent samples t-test. ResultsThere was no significant improvement in the total FTM scores in rTMS compared to the sham stimulation on day 5 (p = 0.132), day 12 (p = 0.574), or day 30 (p = 0.382). Similarly, FTM subscales, including tremor severity rating, motor tasks, and functional disability did not improve significantly after rTMS treatment. Mild headache and local pain were the most frequent adverse events. ConclusionAlthough cerebellar rTMS seems to have acceptable safety when used in ET patients, this study could not prove any efficacy for it in reduction of tremor in these patients. Larger studies are needed to evaluate efficacy of this therapeutic intervention and to provide evidence about the optimal stimulation parameters.

Cerebellar repetitive transcranial magnetic stimulation restores pharyngeal brain activity and swallowing behaviour after disruption by a cortical virtual lesion.

Key points Despite evidence that the human cerebellum has an important role in swallowing neurophysiology, the effects of cerebellar stimulation on swallowing in the disrupted brain have not been explored.In this study, for the first time, the application of cerebellar neurostimulation is characterized in a human model of disrupted swallowing (using a cortical virtual lesion).It is demonstrated that cerebellar stimulation can reverse the suppressed activity in the cortical swallowing system and restore swallowing function in a challenging behavioural task, suggesting the findings may have important therapeutic implications. Repetitive transcranial magnetic stimulation (rTMS) can alter neuronal activity within the brain with therapeutic potential. Low frequency stimulation to the ‘dominant’ cortical swallowing projection induces a ‘virtual‐lesion’ transiently suppressing cortical excitability and disrupting swallowing behaviour. Here, we compared the ability of ipsi‐lesional, contra‐lesional and sham cerebellar rTMS to reverse the effects of a ‘virtual‐lesion’ in health. Two groups of healthy participants (n = 15/group) were intubated with pharyngeal catheters. Baseline pharyngeal motor evoked potentials (PMEPs) and swallowing performance (reaction task) were measured. Participants received 10 min of 1 Hz rTMS to the pharyngeal motor cortex which elicited the largest PMEPs to suppress cortical activity and disrupt swallowing behaviour. Over six visits, participants were randomized to receive 250 pulses of 10 Hz cerebellar rTMS to the ipsi‐lesional side, contra‐lesional side or sham while assessing PMEP amplitude or swallowing performance for an hour afterwards. Compared to sham, active cerebellar rTMS, whether administered ipsi‐lesionally (P = 0.011) or contra‐lesionally (P = 0.005), reversed the inhibitory effects of the cortical ‘virtual‐lesion’ on PMEPs and swallowing accuracy (ipsi‐lesional, P < 0.001, contra‐lesional, P < 0.001). Cerebellar rTMS was able to reverse the disruptive effects of a ‘virtual lesion’. These findings provide evidence for developing cerebellar rTMS into a treatment for post‐stroke dysphagia.

Abstract WP195: Cerebellar Magnetic Stimulation for Long-Lasting Dizziness After Brainstem Stroke

Introduction: Brainstem stroke sometimes causes long-lasting dizziness. A cerebellar control disorder of the vestibulo-ocular reflex (VOR) has been postulated as a mechanism of dizziness in such patients. We conducted a proof-of-principle cohort study to assess the potential efficacy of cerebellar repetitive transcranial magnetic stimulation (rTMS) as treatment for long-lasting post-brainstem stroke dizziness. Methods: We first applied cerebellar rTMS in healthy volunteers (n=11) and showed that cerebellar intermittent theta burst stimulation (iTBS) affected vestibulocerebellar neural activity. Then, we enrolled 11 patients with long-lasting post-brainstem stroke dizziness (lateral medullary infarction, 9; lateral pontine infarction, 1; and lateral pontine hemorrhage, 1), applied cerebellar rTMS (iTBS for 5 days), and followed these patients up for clinical symptoms (Dizziness Handicap Inventory [DHI]), signs (nystagmus), and VOR gain. Results: After rTMS, DHI scores were significantly reduced with disappearance or attenuation of the ipsilesional nystagmus characteristic of the long-lasting post-brainstem stroke dizziness. Reduction in the absolute VOR gain was also associated with reduced DHI scores. Relative cerebellar blood flow to the brainstem, measured in 4 patients, was increased. However, the effects of cerebellar rTMS did not always persist. Conclusion: Our study showed the potential efficacy of cerebellar rTMS for treatment of long-lasting post-brainstem stroke dizziness. Further large-scale randomized studies are warranted to confirm our findings.

Methods for paired-pulse cerebellar-M1 TMS with neuronavigation

Background: Paired-pulse cerebellar brain inhibition (CBI) and cerebellar rTMS studies are inconsistent1. Methods of targeting the cerebellum and coil types used are variable, neuronavigation is difficult, and the availability of cooled double cone coils for cerebellar rTMS treatment protocols is limited.

Cerebellar rTMS to promote motor recovery in hemiparetic stroke patients: a double blind sham controlled randomized controlled trial

The cerebellum is known to be strongly implicated in the functional reorganization of motor networks in stroke patients, especially for gait and balance functions. Repetitive transcranial magnetic stimulation (rTMS) of the cerebellum can be used to enhance these adaptive processes in stroke recovery.

Effects of cerebellar magnetic stimulation on chronic post-lateral medullary infarction dizziness: A proof-of-principle cohort study

Background and purposeLateral medullary infarction (LMI) sometimes causes long-lasting dizziness. Although the precise mechanism of chronic post-LMI dizziness is unknown, a cerebellar control disorder of the vestibulo-ocular reflex (VOR) has been reported in such patients. We conducted a proof-of-principle cohort study to assess the potential efficacy of cerebellar repetitive transcranial magnetic stimulation (rTMS) as treatment for chronic post-LMI dizziness. MethodsWe first applied cerebellar rTMS in healthy volunteers (n = 11) and showed that cerebellar intermittent theta burst stimulation (iTBS) affected vestibulocerebellar neural activity. Then, between September and December 2015, we enrolled six patients (aged≥20 years) with chronic post-LMI dizziness (duration≥6 months), applied cerebellar rTMS (iTBS for 5 days), and followed these patients up for up to 25 months for clinical symptoms (Dizziness Handicap Inventory [DHI]), signs (nystagmus), and VOR gain. ResultsFour of the six patients completed the study without complications. After rTMS, DHI scores were reduced (mean pre-rTMS DHI score minus post-rTMS DHI score was 13.0 [P = 0.036]) with disappearance of the ipsilesional nystagmus characteristic of the post-LMI dizziness. Reduction in the absolute VOR gain (mean pre- rTMS gain minus post-rTMS gain in the ipsilesional direction was 0.135 [P = 0.036] and that in the contralesional direction was 0.137 [P = 0.031]) were also associated with reduced DHI scores. Relative cerebellar blood flow to the brainstem was increased in four of five patients. The effects of cerebellar rTMS did not always persist, and three of four patients elected to undergo more than one rTMS series. The repeat cerebellar rTMS treatments had same beneficial effects. ConclusionOur study showed, for the first time, the potential efficacy of cerebellar rTMS for treatment of chronic post-LMI dizziness. The short duration of the cerebellar rTMS effects can be compensated for by repeating the rTMS treatment every few months. Further large-scale randomized studies are warranted to confirm our findings.

Modulation of Cerebellar-Cortical Connections in Multiple System Atrophy Type C by Cerebellar Repetitive Transcranial Magnetic Stimulation

This study aims at modulating the altered cerebellar-cortical interactions in patients with multiple system atrophy-cerebellar subtype (MSA-C) by using cerebellar repetitive transcranial magnetic stimulation (rTMS). We hypothesized that cerebellar modulation by low-frequency rTMS can resolve the abnormal cortical excitability in multiple system atrophy cerebellar subtype. We studied detailed effects of rTMS of the cerebellum on reaction time (RT) and short-latency afferent inhibition (SAI) response in MSA-C group, Alzheimer Disease (AD) group, and a control group of healthy individuals. The RT and SAI responses were measured before and after 1 Hz cerebellar rTMS in all groups. The study was conducted in the neurophysiology laboratory in Hacettepe University Hospital. Our results indicated that motor cortex disinhibition was predominant in patients with AD and MSA-C. In AD and control groups, there were no changes in SAI after rTMS. However, after application of rTMS over the cerebellum in MSA-C patients, the pathological disinhibition and RT results showed an improvement compared to their previous results. Our study highlights that cerebellar rTMS impairs abnormal cerebellar-cortical inhibitory connections in case of MSA-C.

F149. Low-frequency repetitive transcranial cerebellar magnetic stimulation as an ‘Add-On’ therapy in patients with essential tremor

Introduction ET is a common movement disorder. It is not life threatening, but it can significantly impair patients’ activities of daily living. Beta-blockers and primidone have been used as the treatment of choice for patients with ET. However, up to 50% of ET patients report that they are not satisfied with the improvement of tremor symptoms by these medications. We investigated effect of cerebellar low-frequency repetitive transcranial magnetic stimulation (rTMS) as an ‘add-on’ treatment on patients with Essential tremor (ET). Methods This was a single-center, prospective, sham-controlled and single-blinded study. Fourteen ET patients participated. ET was diagnosed when the patient had bilateral postural or kinetic tremor of the arms, no dystonia and no possibility of drug-induced secondary tremor. In addition, we included subjects in this study only if they had residual significant tremor despite beta-blockers and other drugs as symptomatic management. Subjects were randomized into a group receiving real-rTMS and another group receiving sham-rTMS. rTMS was applied over each side of the cerebellum in turn. The order of the stimulation to each side was randomly assigned. For 5 days, 600 stimulations a day were applied with an intensity of 90% of the resting motor threshold (RMT) with 1-Hz frequency. Clinical tremor rating scale (CTRS) was measured before, a week and 5 weeks after starting day of the rTMS procedure. Results Eight and 6 patients were randomized to the groups of real and sham-rTMS, respectively. The mean age, symptoms duration and baseline CTRS scores were comparable. ANOVA analysis showed that all three parts (A, B and C) of CTRS were not different before, a week and 5 weeks after starting rTMS procedure both in real and sham-rTMS groups. There were no adverse events including headache, dizziness, syncope and seizure. Conclusion Cerebellar low-frequency rTMS is safe but not effective as an ‘add-on’ therapy in patients with ET.

Effectiveness of cerebellar repetitive transcranial magnetic stimulation in essential tremor: study protocol for a randomized, sham-controlled trial

Background: Recent studies have shown that the cerebellum has a significant role in development of essential tremor and repetitive transcranial magnetic stimulation (rTMS) has therapeutic effects on its motor symptoms. Methods/Design: This is a prospective, randomized, triple-blind, sham-controlled, add-on, crossover trial involving patients with essential tremor. Thirty patients will be included and randomized to either real rTMS (900 daily pulses of rTMS over each cerebellar hemisphere) or sham stimulation (low current electrical stimulation). After 2 months of follow-up, patients will undergo crossover and receive the other treatment. For the primary outcome measure, patients will be assessed using Fahn-Tolosa-Marin scale. Adverse events will be assessed as the secondary outcome measure. Discussion: This study evaluates the effect of cerebellar rTMS on tremor severity of patients afflicted with essential tremor, and aims to address the shortcomings of previous studies using a relatively larger sample size and randomized, sham-controlled, crossover design. Trial registration: This trial has been registered at ClinicalTrials.gov (identifier: NCT02704793) on 5 March 2016 and also at Iranian Registry of Clinical Trials (IRCT) (registration ID: IRCT2015100824428N1) on 1 April 2016. Ethics: This study has been approved by the Research Ethics Committee of Mashhad University of Medical Sciences, Iran (approval number: ir.mums.sm.rec.1394.353). Informed consent: Written informed consent will be obtained from all participants.

Clinical effects of non-invasive cerebellar magnetic stimulation treatment combined with neuromotor rehabilitation in traumatic brain injury. A single case study.

Multimodal treatments are emerging as effective approaches for motor recovery in traumatic brain injury (TBI). Various evidence has demonstrated that repetitive transcranial magnetic stimulation (rTMS) may improve outcomes in people with motor disorders. Behavioral gains from rTMS protocols may be maximized when brain stimulation is coupled with carefully designed occupational/physical therapy. We present the case of a 25-year-old man with chronic TBI (a bilateral corticosubcortical parieto-occipital lesion) who underwent three weeks of cerebellar intermittent theta burst stimulation (iTBS), a form of rTMS, combined with neurorehabilitation treatment. The Fugl-Meyer Assessment (FMA), Berg Balance Scale (BBS), Jebsen-Taylor Hand Function Test, and accelerometer gait analysis were administered before and after treatment. The results showed improvements in balance performance (BBS: T0=47; T1=53; +10.72%), motor recovery (FMA: T0=93/100; T1=96/100; +3.00%), step length (T0=50.4±7.2; T1=53.8±2.2 cm, p<0.001), and walking speed (T0=0.87±0.06; T1=0.91±0.04 m/sec,p<0.001). Combined cerebellar rTMS and neurore-Clinical effects of non-invasive cerebellar magnetic stimulation treatment combined with neuromotor rehabilitation in traumatic brain injury. A single case study. habilitation seems to be a promising treatment for motor and balance dysfunctions in TBI patients.

High-frequency focal repetitive cerebellar stimulation induces prolonged increases in human pharyngeal motor cortex excitability.

Neurostimulation is a rapidly emerging approach to swallowing rehabilitation, but cerebellar stimulation has not been explored as a treatment. Such proposed therapies for post-stroke dysphagia have required confirmation of physiological effects and optimisation of parameters in healthy humans prior to translational progression into patient groups. There is strong evidence for a role of the cerebellum in swallowing physiology, but this relationship has been under-explored. Recently, single pulses of cerebellar magnetic stimulation have been shown to directly evoke responses from pharyngeal musculature and produce short-term enhancement of cortico-pharyngeal motor evoked potentials, suggesting the feasibility of a cerebellar approach to neurostimulation in the swallowing system. We therefore examined multiple parameters of repetitive cerebellar magnetic stimulation and have described the optimal settings to provoke longer-lasting changes in swallowing neurophysiology. Based on evidence from the post-stroke dysphagia neurostimulation literature, these changes may have a therapeutic potential for swallowing rehabilitation. Brain neurostimulation has been shown to modulate cortical swallowing neurophysiology in post-stroke dysphagia with therapeutic effects which are critically dependent on the stimulation parameters. Cerebellar neurostimulation is, however, a novel, unexplored approach to modulation of swallowing pathways as a prelude to therapy for dysphagia. Here, we randomised healthy human subjects (n=17) to receive one of five cerebellar repetitive TMS (rTMS) interventions (Sham, 1Hz, 5Hz, 10Hz and 20Hz) on separate visits to our laboratory. Additionally, a subset of subjects randomly received each of three different durations (50, 250, 500 pulses) of optimal frequency versus sham cerebellar rTMS. Prior to interventions subjects underwent MRI-guided single-pulse transcranial magnetic stimulation (TMS) to co-localise pharyngeal and thenar representation in the cortex and cerebellum (midline and hemispheric) before acquisition of baseline motor evoked potential (MEP) recordings from each site as a measure of excitability. Post-interventional MEPs were recorded for an hour and compared to sham using repeated measures ANOVA. Only 10Hz cerebellar rTMS increased cortico-pharyngeal MEP amplitudes (mean bilateral increase 52%, P=0.007) with effects lasting 30min post-intervention with an optimal train length of 250 pulses (P=0.019). These optimised parameters of cerebellar rTMS can produce sustained increases in corticobulbar excitability and may have clinical translation in future studies of neurogenic dysphagia.

71.: Modification of transcranial magnetic stimulation-evoked potentials by cerebellar theta burst stimulation

Repetitive transcranial magnetic stimulation (rTMS) is a potential treatment for neurological disease. Combined transcranial magnetic stimulation and electroencephalography (TMS-EEG) is a relatively new approach to the study of cortical excitability in neurological disease, with the N100 component of the TMS-evoked potential being a marker of intracortical inhibition. Intermittent theta burst stimulation (iTBS) of the cerebellum increases corticospinal excitability in the contralateral primary motor cortex and continuous theta burst stimulation (cTBS) decreases excitability, as reflected in motor evoked potentials (MEP). The purpose of this study was to compare the effects of cTBS on the MEP and N100 potential. TMS-EEG was carried out in 16 healthy volunteers, aged 21–30 years. In each session, MEP were recorded from the left motor cortex. Single TMS pulses were then applied before and after 30 Hz iTBS, cTBS or sham stimulation of the right cerebellar hemisphere stimulus intensity of 80% or 90% of active motor threshold. Further MEP were then recorded. EEG recordings were analysed offline and independent component analysis was used to remove artefact. Mean N100 amplitudes after the three treatments were compared using mixed model analysis of variance, with the pre-treatment N100 amplitudes as covariates. Using a stimulus intensity of 90%, there was an effect of TBS protocol on amplitude of the resting MEP, which was significantly lower after cTBS than sham TBS, F(2, 14) = 4.28, p = 0.035. Cortical silent period (CSP) was increased following iTBS, compared to sham, F(2, 13) = 4.87, p = 0.026), but were not significant for 80% TBS. Combining results of 80% and 90% stimulus intensities, the mean N100 amplitude was significantly greater after iTBS than sham TBS, F(2, 27) = 3.52, p = 0.044. The augmentation of the N100 potential by iTBS is consistent with the increase in the CSP, also a marker of inhibition. Unexpectedly, the reduction in the amplitude of the resting MEP by cTBS was not accompanied by an increase in either the CSP or the N100 amplitude suggesting it arises from decreased facilitation rather than increased intracortical inhibition. These findings are important for predicting the effects of cerebellar rTMS in disease.